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Rational-driver approximation in car-following theory.

The problem of a car following a lead car driven with constant velocity is considered. To derive the governing equations for the following car dynamics a cost functional is constructed. This functional ranks the outcomes of different driving strategies, which applies to fairly general properties of the driver behavior. Assuming rational-driver behavior, the existence of the Nash equilibrium is proved. Rational driving is defined by supposing that a driver corrects continuously the car motion to follow the optimal path minimizing the cost functional. The corresponding car-following dynamics is described quite generally by a boundary value problem based on the obtained extremal equations. Linearization of these equations around the stationary state results in a generalization of the widely used optimal velocity model. Under certain conditions (the "dense traffic" limit) the rational car dynamics comprises two stages, fast and slow. During the fast stage a driver eliminates the velocity difference between the cars, the subsequent slow stage optimizes the headway. In the dense traffic limit an effective Hamiltonian description is constructed. This allows a more detailed nonlinear analysis. Finally, the differences between rational and bounded rational driver behavior are discussed. The latter, in particular, justifies some basic assumptions used recently by the authors to construct a car-following model lying beyond the frameworks of rationality.

Journal Article↗

Statistical mechanics of systems with heterogeneous agents: minority games

We study analytically a simple game theoretical model of heterogeneous interacting agents. We show that the stationary state of the system is described by the ground state of a disordered spin model which is exactly solvable within the simple replica symmetric ansatz. Such a stationary state differs from the Nash equilibrium where each agent maximizes her own utility. The latter turns out to be characterized by a replica symmetry broken structure. Numerical results fully agree with our analytical findings.

Journal Article↗

Stochastic gain in population dynamics.

We introduce an extension of the usual replicator dynamics to adaptive learning rates. We show that a population with a dynamic learning rate can gain an increased average payoff in transient phases and can also exploit external noise, leading the system away from the Nash equilibrium, in a resonancelike fashion. The payoff versus noise curve resembles the signal to noise ratio curve in stochastic resonance. Seen in this broad context, we introduce another mechanism that exploits fluctuations in order to improve properties of the system. Such a mechanism could be of particular interest in economic systems.

Algorithms↗

A study of evolutionary multiagent models based on symbiosis.

Multiagent Systems with Symbiotic Learning and Evolution (Masbiole) has been proposed and studied, which is a new methodology of Multiagent Systems (MAS) based on symbiosis in the ecosystem. Masbiole employs a method of symbiotic learning and evolution where agents can learn or evolve according to their symbiotic relations toward others, i.e., considering the benefits/losses of both itself and an opponent. As a result, Masbiole can escape from Nash Equilibria and obtain better performances than conventional MAS where agents consider only their own benefits. This paper focuses on the evolutionary model of Masbiole, and its characteristics are examined especially with an emphasis on the behaviors of agents obtained by symbiotic evolution. In the simulations, two ideas suitable for the effective analysis of such behaviors are introduced; "Match Type Tile-world (MTT)" and "Genetic Network Programming (GNP)". MTT is a virtual model where tile-world is improved so that agents can behave considering their symbiotic relations. GNP is a newly developed evolutionary computation which has the directed graph type gene structure and enables to analyze the decision making mechanism of agents easily. Simulation results show that Masbiole can obtain various kinds of behaviors and better performances than conventional MAS in MTT by evolution.

Algorithms↗

Effects of financial incentives on the breakdown of mutual trust.

Disagreements between psychologists and economists about the need for and size of financial incentives continue to be hotly discussed. We examine the effects of financial incentives in a class of interactive decision-making situations, called centipede games, in which mutual trust is essential for cooperation. Invoking backward induction, the Nash equilibrium solution for these games is counterintuitive. Our previous research showed that when the number of players in the centipede game is increased from two to three, the game is iterated in time, the players are rematched, and the stakes are unusually high, behavior approaches equilibrium play. Results from the present study show that reducing the size of the stakes elicits dramatically different patterns of behavior. We argue that when mutual trust is involved, the magnitude of financial incentives can induce a considerable difference.

Adult↗

Personal view: 'don't ask, don't tell'--the undesirable consequences of incidental test results in gastroenterology.

A gastroenterologist is frequently approached to perform an endoscopic procedure after an incidental test has resulted in an unexpected positive finding. Should the incidental test result be ignored or automatically followed by an endoscopic procedure? The present analysis strives to characterize the common pattern of such scenarios and resolve their underlying dilemma. A model of game theory is used as a mathematical tool to develop general management strategies. Three clinical scenarios are used as examples to demonstrate this approach. The model is based on how doctors rank the various outcomes with which they are confronted by the incidental test results. The ranks of different outcomes are listed in a decision matrix that is converted into a two-by-two, non-zero, ordinal game. All scenarios of incidental test results emerge as a similar type of game that is best played by both parties adhering to the same set of strategies: 'Don't do the test' and 'don't respond to whatever test result it yields'. These two strategies lead to a Nash equilibrium for a non-zero game, where neither party can improve its payoff any further by choosing a different strategy. Although the equilibrium does not provide the individual players with their best possible payoff, it yields the best overall outcome available to both parties given the economic and medical constraints of the situation.

Gastrointestinal Diseases↗

In vivo imaging of hepatic fatty acid metabolism in patients with non-alcoholic steatohepatitis using semiquantitative 123I-labeled branched-chain fatty acid analog.

Obesity is now prevailing worldwide, coincident with the increase of hepatic steatosis. Metabolic syndrome with obesity and hypertension, hyperlipidemia, and impaired glucose tolerance is one of the most frequent life-threatening diseases and non-alcoholic steatohepatitis is believed to be a hepatic expression of this syndrome. Non-alcoholic steatohepatitis is prevalent and well characterized in Caucasians, but little is known about non-alcoholic steatohepatitis in Asia-Oceania. Obesity will be a serious social problem in Asia-Oceania in the next two decades and we need to prevent the increase of this syndrome. Therefore, it is extremely important to know about non-alcoholic steatohepatitis based on racial differences, because this syndrome is likely to be a multi-factorial syndrome resulting from different combinations of susceptibility genes superimposed on different environmental factors. Because hepatic steatosis is the first step in the development of not only metabolic syndrome but also non-alcoholic steatohepatitis, the genetic background of Japanese NASH patients was investigated and a measure to assess fatty acid beta-oxidation in the liver in vivo was developed.

Animals↗

The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite 'scavenger'?

Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to stimulate N-methyl-D-aspartate (NMDA) receptors to enhance long-term potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels of H2S in the brain are reported to range between 10 and 160 microm. Considerably lower H2S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H2S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H2S 'donor', sodium hydrogen sulfide (NaSH) on peroxynitrite-mediated damage to biomolecules and to cultured human SH-SY5Y cells. H2S significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of alpha1-antiproteinase to a similar extent to reduced glutathione at each concentration tested (30-250 microm). H2S also inhibited peroxynitrite-induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH-SY5Y cells. These data suggest that H2S has the potential to act as an inhibitor of peroxynitrite-mediated processes in vivo and that the potential antioxidant action of H2S deserves further study, given that extracellular GSH levels in the brain are very low.

Cell Line↗

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.

OBJECTIVE: Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center. METHODS: For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade. RESULTS: The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis. CONCLUSION: We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.

Biopsy↗

Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus.

Troglitazone is currently approved for the treatment of diabetes mellitus. Hepatic abnormalities have been reported in up to 1.9% of patients receiving the drug. Severe hepatotoxicity, including the need for liver transplantation, has also been reported in patients treated with troglitazone. Troglitazone has been reported to be beneficial in a small group of patients with nonalcoholic steatohepatitis (NASH). We present a patient with nonalcoholic steatohepatitis and diabetes mellitus who developed severe cholestasis after treatment with troglitazone. The exact mechanism of troglitazone toxicity is unknown, and whether preexisting liver abnormalities increase the incidence of toxicity is speculative. Further data are needed before more widespread use of troglitazone can be recommended for patients with nonalcoholic steatohepatitis.

Adult↗

Contribution of obesity to hepatitis C-related fibrosis progression.

OBJECTIVE: Hepatitis C virus (HCV) disease progression is variable. Identification of factors predictive of rapid progression is an important goal for improving patient management. The aim of this study was to evaluate the predictive role of several variables, including some that are etiologically related to the nonalcoholic steatohepatitis (NASH) syndrome such us obesity, in fibrosis progression in both patients with elevated and normal transaminase levels. METHODS: A total of 114 chronic HCV-infected (HCV-RNA positive) patients were recruited prospectively between 2000 and 2001. All patients had at least one liver biopsy. The annual change in fibrosis stage (fibrosis progression rate) was assessed from the time of presumed infection (fibrosis = 0) among those who had only one biopsy (n = 97) or between two biopsies if these were available (n = 17). Based on published data, we arbitrarily defined a patient as a rapid progressor when the fibrosis progression rate was > 0.2 U/yr. Potential predictors of rapid progression were: age at infection and biopsy, sex, significant alcohol intake (> 50 g/day), risk factor of HCV acquisition (based on answers to a questionnaire), obesity (based on body mass index [BMI]), autoantibodies, iron overload (ferritin, transferrin saturation), diabetes, hyperlipidemia, anti-HBcore IgG, genotype, and viral load. RESULTS: The median fibrosis progression rate was 0.05 U/yr (range 0-1.58 yr). In all, 22 patients (19%) were rapid progressors. Variables associated with progression by multivariate analysis included: advanced age at infection (p = 0.0001), BMI > or = 25 (p = 0.01), and ALT > 1.5 times upper limit of normal (p = 0.01). Among patients with ALT > 1.5 times upper limit of normal, these variables were advanced age at infection, BMI > or = 25, diabetes and transferrin saturation > 45. Among those with normal ALT levels, only BMI > or = 30 was predictive of progression. CONCLUSIONS: Obesity, advanced age at infection, and elevated ALT levels predict rapid disease progression, suggesting that measures aimed at weight reduction may play a significant role in hepatitis C management. The natural history of hepatitis C is independent of the presence of autoimmunity markers.

Adult↗

Gender and ethnic differences in adolescents' attitudes toward condom use.

This secondary analysis from the National Adolescent Student Health Survey (NASHS) examined relationships between adolescents' personal and perceived peer attitudes toward condom use with gender and self-reported ethnic background. Descriptive results revealed general personal support and perceived peer support for condom use. Results from multivariate analysis of variance (MANOVAs) demonstrated significant interaction effects for the eighth grade sample [F = (4, 2383228) = 3530.01 p = .000], and the 10th grade sample [F = (4, 2636878) = 2594.41073, p = .000]. Contrasts revealed significant differences among all ethnic groups for both belief variables for the entire sample, eighth grade students, and 10th grade students. Though general support exists for condom use among U.S. eighth and 10th grade students, conviction varies among groups perhaps indicating a need for tailored messages about condom use, especially for Hispanic students. Implications for health education include the need for cultural-sensitive and gender-sensitive STD education.

Acquired Immunodeficiency Syndrome↗

Promoting emotional health through haiku, a form of Japanese poetry.

This teaching technique can be adapted to use with young children. The use of rhymes may be easier and more fun for younger students. Also, this teaching technique can be used to address numerous health issues, which makes it appropriate for all health content areas. In addition to using student selections that illustrate various emotions, other resources are available for this activity. Libraries and bookstores offer wide selections of books containing poetry and quotations. In addition to books about haiku, consider general poetry selections by Maya Angelou, e.e. cummings, Ogden Nash, and Shel Silverstein. Musical selections can represent different styles, such as the Beatles' "Yesterday"; Blind Melon's "Change"; Garth Brooks' "The Dance"; Eric Clapton's "Tears from Heaven"; Gloria Estefan's "Coming Out of the Dark"; Whitney Houston's "Emotional" and "I Will Always Love You"; and Elton John's "Circle of Life." Internet sites also can be accessed for poetry samples (see Internet Resources). An Internet resource for ordering discounted books, including selections about haiku and poetry, is Amazon.com--Earth's Largest Book store, at http:www.amazon.com/exec/obidos/ subst/home/home.html/0184-8423170-571096.

Child↗

When does "economic man" dominate social behavior?

The canonical model in economics considers people to be rational and self-regarding. However, much evidence challenges this view, raising the question of when "Economic Man" dominates the outcome of social interactions, and when bounded rationality or other-regarding preferences dominate. Here we show that strategic incentives are the key to answering this question. A minority of self-regarding individuals can trigger a "noncooperative" aggregate outcome if their behavior generates incentives for the majority of other-regarding individuals to mimic the minority's behavior. Likewise, a minority of other-regarding individuals can generate a "cooperative" aggregate outcome if their behavior generates incentives for a majority of self-regarding people to behave cooperatively. Similarly, in strategic games, aggregate outcomes can be either far from or close to Nash equilibrium if players with high degrees of strategic thinking mimic or erase the effects of others who do very little strategic thinking. Recently developed theories of other-regarding preferences and bounded rationality explain these findings and provide better predictions of actual aggregate behavior than does traditional economic theory.

Competitive Behavior↗

Detoxification of corn antimicrobial compounds as the basis for isolating Fusarium verticillioides and some other Fusarium species from corn.

The preformed antimicrobial compounds produced by maize, 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one and its desmethoxy derivative 2,4-dihydroxy-2H-1,4-benzoxazin-3-one, are highly reactive benzoxazinoids that quickly degrade to the antimicrobials 6-methoxy-2-benzoxazolinone (MBOA) and 2-benzoxazolinone (BOA), respectively. Fusarium verticillioides (= F. moniliforme) is highly tolerant to MBOA and BOA and can actively transform these compounds to nontoxic metabolites. Eleven of 29 Fusarium species had some level of tolerance to MBOA and BOA; the most tolerant, in decreasing order, were F. verticillioides, F. subglutinans, F. cerealis (= F. crookwellense), and F. graminearum. The difference in tolerance among species was due to their ability to detoxify the antimicrobials. The limited number of species having tolerance suggested the potential utility of these compounds as biologically active agents for inclusion within a semiselective isolation medium. By replacing the pentachloronitrobenzene in Nash-Snyder medium with 1.0 mg of BOA per ml, we developed a medium that resulted in superior frequencies of isolation of F. verticillioides from corn while effectively suppressing competing fungi. Since the BOA medium provided consistent, quantitative results with reduced in vitro and taxonomic efforts, it should prove useful for surveys of F. verticillioides infection in field samples.

Benzoxazoles↗

Gene overexpression, purification, and identification of a desulfurization enzyme from Rhodococcus sp. strain IGTS8 as a sulfide/sulfoxide monooxygenase.

The oxidation of dibenzothiophene to dibenzothiophene sulfone has been linked to the enzyme encoded by the sox/dszC gene from Rhodococcus sp. strain IGTS8 (S. A. Denome, C. Oldfield, L. J. Nash, and K. D. Young, J. Bacteriol. 176:6707-6717, 1994; C. S. Piddington, B. R. Kovacevich, and J. Rambosek, Appl. Environ. Microbiol. 61:468-475, 1995). However, this enzyme has not been characterized, and the type of its catalytic activity remains unclassified. In this work, the sox/dszC gene was overexpressed in Escherichia coli, a procedure for the purification of the expressed enzyme was developed, and the properties of and the reactions catalyzed by the purified enzyme were characterized. This enzyme binds one flavin mononucleotide (Kd, 7 micrometers) or reduced flavin mononucleotide (FMNH2) (Kd < 10(-8) M) per 90,200-Da homodimer, and FMNH2 is an essential cosubstrate for its activity. Patterns of product formation were examined under different FMNH2 availabilities, and results indicate that this enzyme catalyzes a stepwise conversion of dibenzothiophene to the corresponding sulfoxide and subsequently to the sulfone. On the basis of isotope labeling patterns with H2(18)O and 18O2, dibenzothiophene sulfoxide and sulfone obtained their oxygen atom(s) from molecular oxygen rather than water in their formation from dibenzothiophene. The enzyme also utilizes benzyl sulfide and benzyl sulfoxide as substrates. Hence, it is identified as a sulfide/sulfoxide monooxygenase. This monooxygenase is similar to the microsomal flavin-containing monooxygenase but is unique among microbial flavomonooxygenases in its ability to catalyze two consecutive monooxygenation reactions.

Bacterial Proteins↗

A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH.

A glycoprotein encoded by the UL1 gene of herpes simplex virus type 1 (HSV-1) was detected in infected cells with antipeptide sera. The UL1 gene has previously been implicated in virus-induced cell fusion (S. Little and P. A. Schaffer, Virology 112:686-697, 1981). Two protein species, a 30-kDa precursor form and a 40-kDa mature form of the glycoprotein, both of which were modified with N-linked oligosaccharides, were observed. This novel glycoprotein is the 10th HSV-1 glycoprotein to be described and was named glycoprotein L (gL). A complex was formed between gL and gH, a glycoprotein known to be essential for entry of HSV-1 into cells and for virus-induced cell fusion. Previously, it had been reported that gH expressed in the absence of other viral proteins was antigenically abnormal, not processed, and not expressed at the cell surface (U.A. Gompels and A. C. Minson, J. Gen. Virol. 63:4744-4755, 1989; A. J. Forrester, V. Sullivan, A. Simmons, B. A. Blacklaws, G. L. Smith, A. A. Nash, and A. C. Minson, J. Gen. Virol. 72:369-375, 1991). However, gH coexpressed with gL by using vaccinia virus recombinants was antigenically normal, processed normally, and transported to the cell surface. Similarly, gL was dependent on gH for proper posttranslational processing and cell surface expression. These results suggest that it is a hetero-oligomer of gH and gL which is incorporated into virions and transported to the cell surface and which acts during entry of virus into cells.

Amino Acid Sequence↗

Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient mice.

Human gammaherpesvirus infections are associated with development of lymphoproliferative disease. Understanding of the mechanisms of gammaherpesvirus lymphomagenesis during chronic infection in a natural host has been limited by the exquisite species specificity of human gammaherpesviruses and the expense of primates. Murine gammaherpesvirus gammaHV68 is genetically and biologically related to human gammaherpesviruses and herpesvirus saimiri and has been reported to be associated with lymphoproliferative disease in mice (N. P. Sunil-Chandra, J. Arno, J. Fazakerley, and A. A. Nash, Am. J. Pathol. 145:818-826, 1994). We report the development of an animal model of gammaHV68 lymphomagenesis in BALB/c beta2 microglobulin-deficient mice (BALB beta2m-/-). GammaHV68 infection induced two lymphoproliferative lesions: B-cell lymphoma and atypical lymphoid hyperplasia (ALH). ALH lesion histology resembled lesions of Epstein-Barr virus-associated posttransplant lymphoproliferative disease and was characterized by the abnormal infiltration of the white pulp with cells expressing the plasma cell marker CD138. Lymphomas observed in gammaHV68-infected animals were B220+/CD3- large-cell lymphomas. GammaHV68-infected cells were common in ALH lesions as measured by in situ hybridization with a probe specific for viral tRNAs (vtRNAs), but they were scarce in gammaHV68-infected spleens with normal histology. Unlike ALH lesions, gammaHV68 vtRNA-positive cells were rare in lymphomas. GammaHV68 infection of BALB beta2m-/- mice results in lymphoproliferation and lymphoma, providing a valuable tool for identifying viral and host genes involved in gammaherpesvirus-associated malignancies. Our findings suggest that gammaHV68 induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation of chronic inflammation.

Animals↗